Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Expression and integrity of DNA topoisomerase II isoforms does not explaingeneric drug resistance in malignant mesothelioma
Autore:
McLaren, BR; Whitaker, D; Robinson, BWS; Lake, RA;
Indirizzi:
Univ Western Australia, Western Australian Inst Med Res, Queen Elizabeth II Med Ctr, Dept Med, Nedlands, WA 6009, Australia Univ Western Australia Nedlands WA Australia 6009 nds, WA 6009, Australia QEII Med Ctr, PathCtr, Perth, WA, Australia QEII Med Ctr Perth WA Australia I Med Ctr, PathCtr, Perth, WA, Australia
Titolo Testata:
CANCER CHEMOTHERAPY AND PHARMACOLOGY
fascicolo: 1, volume: 48, anno: 2001,
pagine: 1 - 8
SICI:
0344-5704(200107)48:1<1:EAIODT>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLUTATHIONE-S-TRANSFERASE; CANCER CELL-LINES; LUNG-CANCER; PLEURAL MESOTHELIOMA; NONNEOPLASTIC MESOTHELIUM; BREAST-CANCER; ALPHA GENE; DOXORUBICIN; ETOPOSIDE; LEUKEMIA;
Keywords:
mesothelioma; topoisomerase II; etoposide; doxorubicin; drug resistance;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Lake, RA Univ Western Australia, Western Australian Inst Med Res, Queen Elizabeth II Med Ctr, Dept Med, 4th Floor,G Block, Nedlands, WA 6009, Australia Univ Western Australia 4th Floor,G Block Nedlands WA Australia 6009
Citazione:
B.R. McLaren et al., "Expression and integrity of DNA topoisomerase II isoforms does not explaingeneric drug resistance in malignant mesothelioma", CANC CHEMOT, 48(1), 2001, pp. 1-8

Abstract

Purpose: Malignant mesothelioma is a tumour that is highly resistant to a number of different chemotherapy agents, yet the mechanisms by which resistance occurs are poorly understood. The pattern of resistance is consistent with disruption of topoisomerase function or expression. Coupled with this,we have previously noted a common serological reaction to the isoform of topoisomerase IL suggesting that it may be aberrantly expressed in patients with mesothelioma. Methods: We assessed the expression of topoisomerase II isoforms in sections of primary tumour. We tested a panel of five mesothelioma cell lines for sensitivity to the known topoisomerase-targeting drugs, doxorubicin and etoposide. We sequenced expressed segments of the topoisomerase genes from these cell lines that have previously been associated with drug resistance. We then investigated other potential resistance mechanisms. Results: We found that the beta isoform of topoisomerase II was more frequently expressed in primary tumours. Only one of the five cell lines was highly resistant to etoposide and this cell line was found to have a point mutation in the gene for topoisomerase II alpha. Protein levels of topoisomerase II alpha and fl did not correlate with sensitivity to either doxorubicin nor to etoposide. Semiquantitative analysis suggested that there was marked variation in the levels of mRNA expression of MRP, gamma -GCS and MDR1. None of these findings could be associated with resistance to chemotherapy. Conclusion: We conclude that mutations in topoisomerase II alpha can be associated with extreme resistance of mesothelioma to etoposide. The generic drug resistance of this tumour requires further investigation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 00:05:13